The potential role of monoclonal antibodies in the diagnosis and treatment of cancer has been the focus of much recent investigation and speculation. Of particular interest are their use in immunoassays to detect and monitor the course of the disease, for example, during therapy. Also of particular interest are the potential applications of monocolonal antibodies for tumor imaging and therapy due to their capacity to bind tumor-associated antigens in vivo.
Developments in monoclonal antibody technology have also made it possible to investigate the antigenic complexity of human tumors. In particular, the specific immunoreactivity of monoclonal antibodies permits the identification and differentiation of distinct antigens expressed by human tumors. The characterization of such distinct tumor-associated antigens, therefore, provides a means to promote the production and use of monoclonal antibodies for cancer diagnosis and therapy.
Certain antigens are expressed by both human tumor cells and normal cells. These antigens are accordingly referred to not as "tumor specific" but as "tumor-associated" antigens. The diagnostic and therapeutic value of such tumor-associated antigens generally results from the excess quantity of antigen expressed by tumor cells relative to normal cells and the in vivo selectivity of antibodies for antigens expressed by tumor cells over normal cells. The ability of antibodies administered in vivo to localize with specificity at tumor sites is believed to result from: (1) the increased expression of antigen by tumor cells due to the altered and rapid metabolism of malignant growth; and, (2) the increased density of tumor cells and abnormal architecture of tumor sites relative to normal cells in surrounding tissue.
To date, only a limited number of tumor-associated antigens are well characterized. For example, antibodies that react with antigens of various lung carcinomas are described in Varki et. al., "Antigens Associated with a Human Lung Adenocarcinoma Defined by Monoclonal Antibodies," Cancer Research 44:681-687 (1984). According to Varki et. al., monoclonal antibodies KSl/4 and KSl/17 recognize not only three types of lung carcinomas (adenocarcinoma, epidermoid carcinoma and small-cell carcinoma) but also react with colon, breast and stomach carcinomas, while KSl/9 reacts with melanoma and adenocarcinomas of the lung, stomach, and colon. The antigens recognized by KSl/4 and KSl/9 are reported to be firmly attached in the plasma membrane. The monoclonal antibodies described in Brenner et. al., "Monoclonal Antibodies to Human Lung Tumor Antigens Demonstrated by Immunofluorescence and Immunoprecipitation," Cancer Research 42:3187-3192 (1982) recognize antigens located on the membranes of squamous cell carcinoma of the lung. Another human lung tumor-associated antigen from small-cell carcinoma is described in Braatz et. al., "Characterization of a Human Lung Tumor-Associated Antigen and Development of a Radioimmunoassay," Cancer Research 42:849-855 (1982).
Moreover, certain tumor-associated antigens useful as diagnostic or prognostic markers may not be present in all patients or during all stages and manifestations of the disease. Diagnostic discrimination and therapeutic efficacy are, therefore, enhanced by the identification and characterization of more than one tumor-associated antigen expressed by the same tumor tissue. For purposes of cancer diagnosis and therapy, it is desirable to rely on a set or panel of distinct antigens associated with specific types of human tumors. Accordingly, there exists a need for further identification and characterization of unique tumor-associated antigens.